Functional gels that have been conferred with various capabilities, such as a substance retaining ability, an ability to respond to external stimuli and, out of concern for the environment, biodegradability, have recently being attracting attention.
For example, peptide derivatives composed of a combination of a biocomponent such as a peptide chain (hydrophilic moiety) and an alkyl chain (hydrophobic moiety) are expected to see use as starting materials and intermediates in pharmaceutical products and agricultural chemicals, and also, as materials having amphiphilic properties, in gelators, thickeners and the like. For instance, it has been reported that the dipeptide compounds which have a special lipid moiety and are referred to as “2-(naphthalen-2-yloxy)acetic acid”+“glycylglycine or glycylserine, etc.” become hydrogels (Non-Patent Document 1):
Recently, novel lipopeptides composed of glycine or histidine bonded to palmitic acid or the like have been disclosed as such lipopeptide compounds (see, for example, Patent Documents 1 and 2). Methods for the preparation of such lipopeptides that involve solid phase peptide synthesis have been disclosed, although such methods are capable only of synthesizing a small amount of product and are thus poorly suited for mass production.
There has also been reported, as a method involving the liquid phase synthesis of a lipopeptide compound, a reaction for obtaining N-(1-cyanoaceto)-histidine by reacting ethyl 1-cyanoacetate with histidine in the presence of sodium ethoxide (Non-Patent Document 2).
In addition, a method for amidating histidine and an ester compound that involves the use of an enzyme in water has been reported (Non-Patent Document 3).
In the above examples from the literature, with regard not only to histidine (His)-terminated lipopeptide compounds, but also lipopeptide compounds terminating with arginine (Arg), asparagine (Asn), glutamine (Gln), lysine (Lys) or tryptophan (Trp), no cases have been described in which the reaction is carried out in a mixed solvent composed of a non-polar organic solvent and an alcohol solvent.
Patent Document 1: WO 2009/005151
Patent Document 2: WO 2009/005152
Non-Patent Document 1: Z. Yang, B. Xu et al., J. Mater. Chem. 2007, 17, 850-854.
Non-Patent Document 2: Huanan Shifan Daxue Xuebao, Ziran Kexueban (2007), (2), 89-92.
Non-Patent Document 3: Yokozeki, Kenzo; Hara, Seiichi; Journal of Biotechnology (2005), 115 (2), 211-220.